Skip to main content

Main menu

  • Home
  • Current Issue
  • Archive
  • Info for
    • Authors
    • Subscribers
    • Advertisers
    • Editorial Board
  • Other Publications
    • In Vivo
    • Cancer Genomics & Proteomics
    • Cancer Diagnosis & Prognosis
  • More
    • IIAR
    • Conferences
    • 2008 Nobel Laureates
  • About Us
    • General Policy
    • Contact
  • Other Publications
    • Anticancer Research
    • In Vivo
    • Cancer Genomics & Proteomics

User menu

  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Anticancer Research
  • Other Publications
    • Anticancer Research
    • In Vivo
    • Cancer Genomics & Proteomics
  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart
Anticancer Research

Advanced Search

  • Home
  • Current Issue
  • Archive
  • Info for
    • Authors
    • Subscribers
    • Advertisers
    • Editorial Board
  • Other Publications
    • In Vivo
    • Cancer Genomics & Proteomics
    • Cancer Diagnosis & Prognosis
  • More
    • IIAR
    • Conferences
    • 2008 Nobel Laureates
  • About Us
    • General Policy
    • Contact
  • Visit us on Facebook
  • Follow us on Linkedin
Research ArticleClinical Studies

Efficacy of Adjuvant Chemotherapy According to the Classification of Recurrence Risk Based on Systemic Inflammatory Markers in Patients With Liver Metastases of Colorectal Cancer

MASATSUNE SHIBUTANI, HISASHI NAGAHARA, TATSUNARI FUKUOKA, YASUHITO ISEKI, KOSEI HIRAKAWA and MASAICHI OHIRA
Anticancer Research September 2019, 39 (9) 5039-5045; DOI: https://doi.org/10.21873/anticanres.13695
MASATSUNE SHIBUTANI
Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: fbxbj429@ybb.ne.jp
HISASHI NAGAHARA
Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
TATSUNARI FUKUOKA
Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
YASUHITO ISEKI
Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
KOSEI HIRAKAWA
Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
MASAICHI OHIRA
Department of Gastroenterological Surgery, Osaka City University Graduate School of Medicine, Osaka, Japan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Background/Aim: Although complete resection of liver metastases colorectal cancer (CLM) is the only potentially curative treatment, surgery alone is not enough, as the recurrence rate after resection is high. Therefore, in clinical practice, adjuvant chemotherapy is performed after resection of CLM. However, the evidence supporting the efficacy of such adjuvant chemotherapy is not sufficient. Previous reports have noted that adjuvant chemotherapy after resection of CLM is effective only in patients with a high risk of recurrence. The purpose of this study was to classify the risk of recurrence using systemic inflammatory markers reportedly associated with clinical outcomes in patients with various types of malignancies, and evaluate the efficacy of adjuvant chemotherapy according to the risk of recurrence. Patients and Methods: The medical records of 119 patients with CLM who underwent potentially curative surgery between 1996 and 2017 were retrospectively reviewed. Preoperative blood samples were obtained within 2 weeks before resection of CLM. was calculated from the blood samples Dividing the serum C-reactive protein level by the serum albumin level derived the C-reactive protein-to-albumin ratio (CAR), reflecting the risk of recurrence. The optimal cut-off value of the CAR was determined according to receiver operating characteristic curve analysis, and then the patients were classified into the high-CAR (high recurrence risk) or low-CAR (low recurrence risk) group. The relationship between the CAR and relapse-free survival after resection of CLM was examined and the efficacy of adjuvant chemotherapy according to the risk of recurrence was evaluated. Results: The cut-off value of the CAR was set at 0.0471. The relapse-free survival rate was significantly better in the low-CAR group than in the high-CAR group. Efficacy of adjuvant chemotherapy after resection of CLM was not recognized in the low-CAR group, whereas the relapse-free survival rates were significantly better for patients who were treated with adjuvant chemotherapy after resection of CLM in the high-CAR group. Conclusion: The preoperative CAR, as a systemic inflammatory marker, was found to be useful as a prognostic marker in patients with CLM who were treated with potentially curative resection. Furthermore, it was suggested that adjuvant chemotherapy after resection of CLM may be effective for preventing recurrence in patients with high levels of inflammatory markers who have a high risk of recurrence.

  • Colorectal cancer liver metastasis
  • adjuvant chemotherapy
  • systemic inflammatory markers
  • C-reactive protein-to-albumin ratio

Treatment of colorectal cancer liver metastasis (CLM) is crucial for improving the prognosis of colorectal cancer (CRC), as the liver is the most common site of metastasis of CRC (1). Although complete resection is the only potentially curative treatment and the most effective treatment in patients with CLM (2-5), surgery alone is not enough, as the rate of recurrence after resection of CLM is very high (70-80%) (6-8). Therefore, in clinical practice, adjuvant chemotherapy is performed after resection of CLM. However, evidence supporting the efficacy of adjuvant chemotherapy after resection of CLM is not sufficient at present.

Although there have been a few reports showing the efficacy of adjuvant chemotherapy after resection of CLM, its effects were limited, as it was shown effective in prolonging relapse-free survival but not in improving overall survival (9-12). In previous reports on the significance of adjuvant chemotherapy after resection of CLM, adjuvant chemotherapy after resection has been found to be more effective for patients with a higher risk of recurrence than for those with a lower risk (9, 13). In clinical practice, adjuvant chemotherapy is often provided for patients who are considered to have a high risk of recurrence (14).

The purpose of this study was to classify the risk of recurrence using systemic inflammatory markers which have been reported to be associated with clinical outcomes in patients with various types of malignancies, and evaluate the efficacy of adjuvant chemotherapy according to the risk of recurrence.

Patients and Methods

Patients. We retrospectively reviewed the medical records of 119 patients who underwent complete macroscopic and microscopic (R0) resection of CLM at Osaka City University Hospital between January 1996 and December 2017. All patients enrolled in this study had undergone resection of CLM for the first time. Patients who had extrahepatic metastasis were excluded from this study.

This retrospective study was approved by the Ethics Committee of the Osaka City University (approval number: 4182) and conducted in accordance with the Declaration of Helsinki. All patients provided their written informed consent.

Methods. Pretreatment blood samples were obtained within 2 weeks before resection of CLM. The C-reactive protein (CRP)-to-albumin ratio (CAR) was calculated from the blood samples by dividing the serum CRP level by the serum albumin level. The optimal cut-off value of the CAR was determined based on receiver operating characteristic (ROC) curve analysis, and patients were classified based on this value into the high-CAR group or the low-CAR group. The modified Glasgow prognostic score (mGPS) was defined according to the methods of a previous report (15) using the combination of the serum CRP and albumin levels: Patients with a CRP level of <1.0 mg/dl were allocated a score of 0; those in whom the CRP and albumin levels were ≥1.0 mg/dl and ≥3.5 g/dl, respectively, were allocated a score of 1; and those in whom the CRP and albumin levels were ≥1.0 mg/dl and albumin <3.5 g/dl, respectively, were allocated a score of 2.

Adverse events were graded using Common Terminology Criteria for Adverse Events (Version 4.03) (16). The worst grade for each adverse event was recorded.

Statistical analyses. The chi-square test, Fisher's exact test and Mann–Whitney U-test were used to analyze the significance of correlations between the CAR and the clinicopathological factors, and the significance of correlations between the chemotherapeutic regimens and the tolerance of chemotherapy. Relapse-free survival was defined as the interval between the date of resection of CLM and the date of the diagnosis of the first recurrence, death from any cause or last follow-up. Survival curves were made using the Kaplan–Meier method. Differences in the survival curves were assessed using the log-rank test. A multivariate Cox proportional hazards model was used to evaluate the prognostic factors associated with the survival. Factors with a p-value of less than 0.1 on the univariate analysis were included in the multivariate analysis.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table I.

Patient characteristics.

All of the statistical analyses were performed using SPSS statistical software program, version 19.0 (IBM Corp., Armonk, NY, USA). A value of p<0.05 was considered to indicate a statistically significant difference.

Results

Patient characteristics. The patient characteristics are summarized in Table I. The study cohort included 65 males and 54 females, with a median age of 65 years (range=22-87 years). Fifty-three patients had synchronous CLM. Sixty-eight patients had a single CLM. Eighty-three patients (69.7%) received adjuvant chemotherapy. The distribution of the regimen of adjuvant chemotherapy was as follows: Single-agent therapy with fluoropyrimidines, such as 5-fluorouracil plus leucovorin, capecitabine, tegafur-uracil/ leucovorin, or S-1: 59 patients; combination therapy with fluoropyrimidines and oxaliplatin, such as 5-fluorouracil with leucovorin and oxaliplatin, or and capecitabine with oxaliplatin: 24 patients.

Figure 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1.

Receiver operating characteristic curve analysis of the C-reactive protein to albumin ratio. Area under the curve=0.601; 95% confidence interval=0.500-0.703; p=0.058.

Classifications according to preoperative inflammatory markers. the CAR, which was a continuous variable, was used as the test variable, and the median relapse-free survival time (14.1 months) as the state variable. The ROC curve analysis of the preoperative CAR suggested an appropriate cut-off of 0.0471, with an area under the curve of 0.601 (95% confidence interval: 0.500-0.703, and sensitivity of 62.0% and specificity of 58.5% (Figure 1). Thus, 0.0471 was adopted as the cut-off value of preoperative CAR, and the patients were classified into the high-CAR group (n=53) or low-CAR group (n=66) accordingly. Based on the definition of the mGPS, 109 patients were classified as having a score of 0, nine as having a score of 1, and one as having a score of 2.

Survival analysis based on the CAR. The relapse-free survival rate was significantly worse in the high-CAR group than in the low-CAR group (p=0.0157) (Figure 2). Similarly, the relapse-free survival rate was significantly worse in patients with a high mGPS than in those with an mGPS of 0 (p<0.0001) (Figure 2).

Correlation between the CAR and clinicopathological factors. The correlation between the CAR and the clinicopathological factors is shown in Table II. When compared to the low-CAR group, the high-CAR group had a significantly larger number of CLM. However, there were no significant differences in other factors.

Figure 2.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 2.

Kaplan–Meier curves for relapse-free survival after resection of colorectal cancer liver metastasis according to C-reactive protein-to-albumin ratio (CAR) (A) and modified Glasgow prognostic score (mGPS) (B). The relapse-free survival rate was significantly worse in the group with a high CAR than in that with a low CAR and in patients with a higher mGPS than in those with a low mGPS.

Correlation between the CAR and the location of recurrence after resection of CLM. No significant differences were observed in the location of the first recurrence after resection of CLM between the high-CAR group and the low-CAR group (Table III).

Efficacy of adjuvant chemotherapy after resection of CLM according to the CAR. Efficacy of adjuvant chemotherapy after resection of CLM was not recognized in the low-CAR group, with a low risk of recurrence, whereas adjuvant chemotherapy provided a significant relapse-free survival benefit in the high-CAR group, with a high risk of recurrence (Figure 3).

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table II.

The correlation between the C-reactive protein-to-albumin ratio (CAR) and clinicopathological factors of patients with liver metastasis of colorectal cancer (CLM).

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table III.

The correlation between the C-reactive protein-to-albumin ratio (CAR and the location of recurrence after resection of liver metastasis of colorectal cancer.

Survival analysis according to chemotherapeutic regimen, limited to the group with a high-CAR. We then performed a sub-group analysis limited to the high-CAR group, with a high risk of recurrence (Figure 4). Among these patients, the relapse-free survival rates were significantly better in both the single-agent therapy group and the combination therapy group than in the no-adjuvant therapy group. However, no significant differences were observed in the relapse-free survival rates between the single-agent therapy group and the combination therapy group.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table IV.

A comparison of the feasibility of adjuvant monotherapy and doublet therapy.

Feasibility assessment of adjuvant chemotherapy. No significant differences were observed in the completion rate or relative dose intensity between the single-agent therapy group and the combination therapy group. However, the incidence of grade 3 or more adverse events was significantly higher in the combination therapy group than in the single-agent therapy group (66.7% vs. 14.8%, p=0.020) (Table IV).

Discussion

In this study, we investigated the prognostic significance of systemic inflammatory markers, such as the CAR and mGPS, for predicting the prognosis in patients with CLM who underwent a potentially curative operation.

Systemic inflammatory markers have been reported to be associated with clinical outcomes, such as the survival time after an operation and the chemotherapeutic efficacy, in patients with various types of malignancies, including CRC (17, 18). However, to our knowledge, this is the first report regarding the correlation between the CAR and prognosis after resection of CLM. As systemic inflammation has been reported to promote proliferation, invasion and metastasis (19-21), preoperative systemic inflammation is considered to provide a favorable environment for the development of micrometastases, resulting in an increasing risk of recurrence.

Both the CAR and mGPS are systemic inflammatory markers that can be calculated from the serum CRP and albumin concentrations. However, most patients are classified into the group with a low risk of recurrence when using the mGPS, as mentioned in previous reports (22-24). In the present study, 91.6% of patients were classified as having an mGPS of 0, which is associated with a better prognosis. Therefore, the CAR is more useful for clinical application than the mGPS in terms of well-balanced risk classification.

Figure 3.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 3.

Kaplan–Meier survival curves for relapse-free survival after resection of colorectal cancer liver metastasis according to treatment with adjuvant chemotherapy or surgery alone for the group with a low C-reactive protein-to-albumin ratio (CAR) (A) and with a high CAR (B). No significant differences were observed in the relapse-free survival between the group treated with surgery-alone and the adjuvant chemotherapy group (p =0.4100) for those with a low CAR. However, in the analysis of the high-CAR group, the relapse-free survival rate was significantly better in the group treated with adjuvant chemotherapy than in that which underwent surgery alone.

Furthermore, the results of this study suggested that adjuvant chemotherapy after resection of CLM was effective only in patients with a high risk of recurrence and that the CAR was useful for risk classification. Although no significant relationships were observed between the relapse-free survival rate and adjuvant chemotherapy in the group with a low risk of recurrence (low CAR), adjuvant chemotherapy helped prolong the relapse-free survival in the group, with a high risk of recurrence (high CAR). Therefore, not all patients who undergo resection of CLM need adjuvant chemotherapy, and it may be better to administer adjuvant chemotherapy only to those with a high risk of recurrence.

Figure 4.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 4.

The Kaplan–Meier survival curves for the relapse-free survival in an analysis limited to the group with a high C-reactive protein-to-albumin ratio (CAR) according to treatment. The relapse-free survival rates were significantly better in both the single-agent therapy group and the combination therapy group than in the group treated with surgery alone (p=0.0017, p=0.0094, respectively). However, no significant differences were observed in the relapse-free survival rates between the single-agent therapy group and the combination therapy group (p=0.5238).

In addition, we compared the chemotherapeutic efficacy of each regimen of adjuvant chemotherapy. In the analysis limited to the high-CAR group, with a high risk of recurrence, both single-agent therapy and combination therapy were effective in preventing the recurrence, and there was no significant difference in the efficacy between these two regimens. We hypothesized that the efficacy of combination therapy would not exceed that of single-agent therapy because the patients treated with combination therapy might receive an insufficient dose of their drug due to their poor condition after resection of CLM. However, no significant differences were observed regarding the relative dose intensity or completion rate between the single-agent therapy group and the combination therapy group, although the incidence of grade 3 or more adverse events was higher in the combination therapy group than in the single-agent therapy group. It is hard to conclude that the additional effect of oxaliplatin in adjuvant chemotherapy after resection of CLM is poor based on the results of this study alone. However, the efficacy of single-agent therapy and that of combination therapy may be equivalent, and single-agent therapy may therefore be sufficient as adjuvant chemotherapy after resection of CLM.

Several limitations associated with the present study warrant mentioning. Firstly, the current study was a retrospective study with a small cohort conducted at a single center. Therefore, the cut-off value of the CAR used in this study was a provisional value. A large, prospective study should be performed to confirm our findings and determine the appropriate cut-off value of the CAR, although it may be difficult to conduct such a study because there are not many cases of curative resection of CLM. Secondly, the endpoint assessed in this study was relapse-free survival. The present study enrolled patients who underwent resection of CLM as long as 20 years ago. With the development of new cytotoxic and molecular-targeted therapies, the survival time after recurrence has been significantly prolonged compared to 20 years ago. Therefore, we assessed only relapse-free survival, not overall survival. However, not only relapse-free survival time, but also overall survival time may have to be assessed when evaluating the efficacy of adjuvant chemotherapy.

Conclusion

The preoperative systemic inflammatory markers were found to be useful as prognostic markers in patients with CLM who were treated with potentially curative resection. Furthermore, it was suggested that adjuvant chemotherapy after resection of CLM may be effective for preventing recurrence in patients with high levels of inflammatory markers who have a high risk of recurrence.

Footnotes

  • Authors' Contributions

    MS designed the study, performed the statistical analysis and draft the article. HN, TF and YI collected the clinical data and revised the article critically. KH and MO designed the study and critically reviewed the article. All Authors read and approved the final article.

  • Conflicts of Interest

    The Authors declare that they have no competing interests in regard to this study.

  • Received July 25, 2019.
  • Revision received August 11, 2019.
  • Accepted August 19, 2019.
  • Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved

References

  1. ↵
    1. Watanabe T,
    2. Muro K,
    3. Ajioka Y,
    4. Hashiguchi Y,
    5. Ito Y,
    6. Saito Y,
    7. Hamaguchi T,
    8. Ishida H,
    9. Ishiguro M,
    10. Ishihara S,
    11. Kanemitsu Y,
    12. Kawano H,
    13. Kinugasa Y,
    14. Kokudo N,
    15. Murofushi K,
    16. Nakajima T,
    17. Oka S,
    18. Sakai Y,
    19. Tsuji A,
    20. Uehara K,
    21. Ueno H,
    22. Yamazaki K,
    23. Yoshida M,
    24. Yoshino T,
    25. Boku N,
    26. Fujimori T,
    27. Itabashi M,
    28. Koinuma N,
    29. Morita T,
    30. Nishimura G,
    31. Sakata Y,
    32. Shimada Y,
    33. Takahashi K,
    34. Tanaka S,
    35. Tsuruta O,
    36. Yamaguchi T,
    37. Yamaguchi N,
    38. Tanaka T,
    39. Kotake K,
    40. Sugihara K,
    41. Japanese Society for Cancer of the Colon and Rectum
    : Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines 2016 for the treatment of colorectal cancer. Int J Clin Oncol 23(1): 1-34, 2017. PMID: 28349281. DOI: 10.1007/s10147-017-1101-6
    OpenUrl
  2. ↵
    1. Fong Y,
    2. Fortner J,
    3. Sun RL,
    4. Brennan MF,
    5. Blumgart LH
    : Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg 230(3): 309-318, 1999. PMID: 10493478. DOI: 10.1097/00000658-199909000-00004
    OpenUrlCrossRefPubMed
    1. Jaeck D,
    2. Bachellier P,
    3. Guiguet M,
    4. Boudjema K,
    5. Vaillant JC,
    6. Balladur P,
    7. Nordlinger B
    : Long-term survival following resection of colorectal hepatic metastases. Association Française de Chirurgie. Br J Surg 84(7): 977-980, 1997. PMID: 9240140
    OpenUrlCrossRefPubMed
    1. Nordlinger B,
    2. Guiguet M,
    3. Vaillant JC,
    4. Balladur P,
    5. Boudjema K,
    6. Bachellier P,
    7. Jaeck D
    : Surgical resection of colorectal carcinoma metastases to the liver. A prognostic scoring system to improve case selection, based on 1568 patients. Association Française de Chirurgie. Cancer 77(7): 1254-1262, 1996. PMID: 8608500
    OpenUrlCrossRefPubMed
  3. ↵
    1. Adam R,
    2. De Gramont A,
    3. Figueras J,
    4. Guthrie A,
    5. Kokudo N,
    6. Kunstlinger F,
    7. Loyer E,
    8. Poston G,
    9. Rougier P,
    10. Rubbia-Brandt L,
    11. Sobrero A,
    12. Tabernero J,
    13. Teh C,
    14. Van Cutsem E
    ; Jean-Nicolas Vauthey of the EGOSLIM (Expert Group on OncoSurgery management of LIver Metastases) group: The OncoSurgery approach to managing liver metastases from colorectal cancer: A multidisciplinary international consensus. Oncologist 17(10): 1225-1239, 2012. PMID: 22962059. DOI: 10.1634/theon cologist.2012-0121
    OpenUrlAbstract/FREE Full Text
  4. ↵
    1. Abdalla EK,
    2. Vauthey JN,
    3. Ellis LM,
    4. Ellis V,
    5. Pollock R,
    6. Broglio KR,
    7. Hess K,
    8. Curley SA
    : Recurrence and outcomes following hepatic resection, radiofrequency ablation, and combined resection/ablation for colorectal liver metastases. Ann Surg 239(6): 825-827, 2004. PMID: 15166961. DOI: 10.1097/01.sla. 0000128305.90650.71
    OpenUrl
    1. Beppu T,
    2. Sakamoto Y,
    3. Hasegawa K,
    4. Honda G,
    5. Tanaka K,
    6. Kotera Y,
    7. Nitta H,
    8. Yoshidome H,
    9. Hatano E,
    10. Ueno M,
    11. Takamura H,
    12. Baba H,
    13. Kosuge T,
    14. Kokudo N,
    15. Takahashi K,
    16. Endo I,
    17. Wakabayashi G,
    18. Miyazaki M,
    19. Uemoto S,
    20. Ohta T,
    21. Kikuchi K,
    22. Yamaue H,
    23. Yamamoto M,
    24. Takada T
    : A nomogram predicting disease-free survival in patients with colorectal liver metastases treated with hepatic resection: multicenter data collection as a Project Study for Hepatic Surgery of the Japanese Society of Hepato-Biliary-Pancreatic Surgery. J Hepatobiliary Pancreat Sci 19(1): 72-84, 2012. PMID: 22020927. DOI: 10.1007/s00534-011-0460-z
    OpenUrlCrossRefPubMed
  5. ↵
    1. Jones RP,
    2. Jackson R,
    3. Dunne DF,
    4. Malik HZ,
    5. Fenwick SW,
    6. Poston GJ,
    7. Ghaneh P
    : Systematic review and meta-analysis of follow-up after hepatectomy for colorectal liver metastases. Br J Surg 99(4): 477-486, 2012. PMID: 22261895. DOI: 10.1002/bjs.8667
    OpenUrlPubMed
  6. ↵
    1. Hasegawa K,
    2. Saiura A,
    3. Takayama T,
    4. Miyagawa S,
    5. Yamamoto J,
    6. Ijichi M,
    7. Teruya M,
    8. Yoshimi F,
    9. Kawasaki S,
    10. Koyama H,
    11. Oba M,
    12. Takahashi M,
    13. Mizunuma N,
    14. Matsuyama Y,
    15. Watanabe T,
    16. Makuuchi M,
    17. Kokudo N
    : Adjuvant oral uracil-tegafur with leucovorin for colorectal cancer liver metastases: A randomized controlled trial. PLoS One 11(9): e0162400, 2016. PMID: 27588959. DOI: 10.1371/journal.pone.0162400
    OpenUrl
    1. Kemeny N,
    2. Huang Y,
    3. Cohen AM,
    4. Shi W,
    5. Conti JA,
    6. Brennan MF,
    7. Bertino JR,
    8. Turnbull AD,
    9. Sullivan D,
    10. Stockman J,
    11. Blumgart LH,
    12. Fong Y
    : Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer. N Engl J Med 341(27): 2039-2048, 1999. PMID: 10615075. DOI: 10.1056/NEJM199912303412702
    OpenUrlCrossRefPubMed
    1. Portier G,
    2. Elias D,
    3. Bouche O,
    4. Rougier P,
    5. Bosset JF,
    6. Saric J,
    7. Belghiti J,
    8. Piedbois P,
    9. Guimbaud R,
    10. Nordlinger B,
    11. Bugat R,
    12. Lazorthes F,
    13. Bedenne L
    : Multicenter randomized trial of adjuvant fluorouracil and folinic acid compared with surgery alone after resection of colorectal liver metastases: FFCD ACHBTH AURC 9002 trial. J Clin Oncol 24(31): 4976-4982, 2006. PMID: 17075115. DOI: 10.1200/JCO.2006.06.8353
    OpenUrlAbstract/FREE Full Text
  7. ↵
    1. Nordlinger B,
    2. Sorbye H,
    3. Glimelius B,
    4. Poston GJ,
    5. Schlag PM,
    6. Rougier P,
    7. Bechstein WO,
    8. Primrose JN,
    9. Walpole ET,
    10. Finch-Jones M,
    11. Jaeck D,
    12. Mirza D,
    13. Parks RW,
    14. Collette L,
    15. Praet M,
    16. Bethe U,
    17. Van Cutsem E,
    18. Scheithauer W,
    19. Gruenberger T,
    20. EORTC Gastro-Intestinal Tract Cancer Group,
    21. Cancer Research UK,
    22. Arbeitsgruppe Lebermetastasen und-tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie (ALM-CAO),
    23. Australasian Gastro-Intestinal Trials Group (AGITG),
    24. Fédération Francophone de Cancérologie Digestive (FFCD)
    : Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): A randomised controlled trial. Lancet 371(9617): 1007-1016, 2008. PMID: 18358928. DOI: 10.1016/S0140-6736(08)60455-9
    OpenUrlCrossRefPubMed
  8. ↵
    1. Kobayashi S,
    2. Beppu T,
    3. Honda G,
    4. Yamamoto M,
    5. Takahashi K,
    6. Endo I,
    7. Hasegawa K,
    8. Kotake K,
    9. Itabashi M,
    10. Hashiguchi Y,
    11. Kotera Y,
    12. Sakamoto K,
    13. Yamaguchi T,
    14. Morita S,
    15. Tabuchi K,
    16. Miyazaki M,
    17. Sugihara K
    : Survival benefit of and indications for adjuvant chemotherapy for resected colorectal liver metastases–a Japanese nationwide survey. J Gastrointest Surg [Epub ahead of print] 2019. PMID: 31197683. DOI: 10.1007/s11605-019-04250-9.
  9. ↵
    1. Nishioka Y,
    2. Moriyama J,
    3. Matoba S,
    4. Kuroyanagi H,
    5. Hashimoto M,
    6. Shindoh J
    : Prognostic impact of adjuvant chemotherapy after hepatic resection for synchronous and early metachronous colorectal liver metastases. Dig Surg 35(3): 187-195, 2018. PMID: 28848205. DOI: 10.1159/000478791
    OpenUrl
  10. ↵
    1. Petrelli F,
    2. Barni S,
    3. Coinu A,
    4. Bertocchi P,
    5. Borgonovo K,
    6. Cabiddu M,
    7. Ghilardi M,
    8. Zaniboni A
    : The modified Glasgow Prognostic Score and survival in colorectal cancer: A pooled analysis of the literature. Rev Recent Clin Trials 10(2): 135-141, 2015. PMID: 25778832
    OpenUrlCrossRefPubMed
  11. ↵
    1. Department of Health and Human Services,
    2. National Institutes of Health,
    3. National Cancer Institute
    . Common terminology criteria for adverse events (CTCAE) v4.03. 2010. Available from http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf.
  12. ↵
    1. Shibutani M,
    2. Maeda K,
    3. Nagahara H,
    4. Noda E,
    5. Ohtani H,
    6. Nishiguchi Y,
    7. Hirakawa K
    : A high preoperative neutrophil-to-lymphocyte ratio is associated with poor survival in patients with colorectal cancer. Anticancer Res 33(8): 3291-3294, 2013. PMID: 23898094. DOI: 10.3748/wjg.v21.i34.9966
    OpenUrlAbstract/FREE Full Text
  13. ↵
    1. Shibutani M,
    2. Nagahara H,
    3. Fukuoka T,
    4. Iseki Y,
    5. Matsutani S,
    6. Wang EN,
    7. Maeda K,
    8. Hirakawa K,
    9. Ohira M
    : Prognostic significance of the C-reactive protein-to-albumin ratio in patients with metastatic colorectal cancer treated with trifluridine/thymidine phosphorylase inhibitor as later-line chemotherapy. Anticancer Res 39(2): 1051-1057, 2019. PMID: 30711994. DOI: 10.21873/anticanres.13212.
    OpenUrlAbstract/FREE Full Text
  14. ↵
    1. Coussens LM,
    2. Werb Z
    . Inflammation and cancer. Nature 420(6917): 860-867, 2002. PMID: 12490959. DOI: 10.1038/nature01322
    OpenUrlCrossRefPubMed
    1. Mantovani C,
    2. Levra NG,
    3. Filippi AR,
    4. Novello S,
    5. Buffoni L,
    6. Ragona R,
    7. Ricardi U
    : Postoperative radiotherapy for patients with completely resected pathologic N2 non-small-cell lung cancer: A retrospective analysis. Clin Lung Cancer 14(2): 194-199, 2013. PMID: 22885347. DOI: 10.1016/j.cllc.2012.05.007
    OpenUrl
  15. ↵
    1. Chiang AC,
    2. Massagué J
    : Molecular basis of metastasis. N Engl J Med 359(26): 2814-2823, 2008. PMID: 19109576. DOI: 10.1056/NEJMra0805239.
    OpenUrlCrossRefPubMed
  16. ↵
    1. Furukawa K,
    2. Shiba H,
    3. Haruki K,
    4. Fujiwara Y,
    5. Iida T,
    6. Mitsuyama Y,
    7. Ogawa M,
    8. Ishida Y,
    9. Misawa T,
    10. Yanaga K
    : The Glasgow prognostic score is valuable for colorectal cancer with both synchronous and metachronous unresectable liver metastases. Oncol Lett 4(2): 324-328, 2012. PMID: 22844378. DOI: 10.3892/ol.2012.722
    OpenUrlPubMed
    1. Sugimoto K,
    2. Komiyama H,
    3. Kojima Y,
    4. Goto M,
    5. Tomiki Y,
    6. Sakamoto K
    : Glasgow prognostic score as a prognostic factor in patients undergoing curative surgery for colorectal cancer. Dig Surg 29(6): 503-509, 2012. PMID: 23392422. DOI: 10.1159/000346002
    OpenUrl
  17. ↵
    1. Shibutani M,
    2. Maeda K,
    3. Nagahara H,
    4. Iseki Y,
    5. Hirakawa K,
    6. Ohira M
    : The significance of the C-reactive protein to albumin ratio as a marker for predicting survival and monitoring chemotherapeutic effectiveness in patients with unresectable metastatic colorectal cancer. Springerplus 5(1): 1798, 2016. PMID: 27812440. DOI: 10.1186/s40064-016-3529-y
    OpenUrl
PreviousNext
Back to top

In this issue

Anticancer Research: 39 (9)
Anticancer Research
Vol. 39, Issue 9
September 2019
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
  • Back Matter (PDF)
  • Ed Board (PDF)
  • Front Matter (PDF)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on Anticancer Research.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Efficacy of Adjuvant Chemotherapy According to the Classification of Recurrence Risk Based on Systemic Inflammatory Markers in Patients With Liver Metastases of Colorectal Cancer
(Your Name) has sent you a message from Anticancer Research
(Your Name) thought you would like to see the Anticancer Research web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
17 + 3 =
Solve this simple math problem and enter the result. E.g. for 1+3, enter 4.
Citation Tools
Efficacy of Adjuvant Chemotherapy According to the Classification of Recurrence Risk Based on Systemic Inflammatory Markers in Patients With Liver Metastases of Colorectal Cancer
MASATSUNE SHIBUTANI, HISASHI NAGAHARA, TATSUNARI FUKUOKA, YASUHITO ISEKI, KOSEI HIRAKAWA, MASAICHI OHIRA
Anticancer Research Sep 2019, 39 (9) 5039-5045; DOI: 10.21873/anticanres.13695

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Reprints and Permissions
Share
Efficacy of Adjuvant Chemotherapy According to the Classification of Recurrence Risk Based on Systemic Inflammatory Markers in Patients With Liver Metastases of Colorectal Cancer
MASATSUNE SHIBUTANI, HISASHI NAGAHARA, TATSUNARI FUKUOKA, YASUHITO ISEKI, KOSEI HIRAKAWA, MASAICHI OHIRA
Anticancer Research Sep 2019, 39 (9) 5039-5045; DOI: 10.21873/anticanres.13695
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Patients and Methods
    • Results
    • Discussion
    • Conclusion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • A Disease-specific Score for Estimating Survival After Irradiation of Bone Metastases from Colorectal Cancer
  • Google Scholar

More in this TOC Section

  • The Systemic Inflammation Score Is an Independent Prognostic Factor for Esophageal Cancer Patients who Receive Curative Treatment
  • Impact of Cytoreductive Nephrectomy Following Nivolumab Plus Ipilimumab Therapy for Patients With Advanced Renal Cell Carcinoma
  • Usefulness of Prophylactic Administration of Pegfilgrastim for Esophageal Cancer Chemotherapy: A Single-center Retrospective Study
Show more Clinical Studies

Similar Articles

Keywords

  • Colorectal cancer liver metastasis
  • Adjuvant chemotherapy
  • systemic inflammatory markers
  • C-reactive protein-to-albumin ratio
Anticancer Research

© 2022 Anticancer Research

Powered by HighWire